The goal of the proposed project is to investigate the relative importance of neural control and local autoregulatory mechanisms in determining vascular smooth muscle (VSM) tone and tissue perfusion in the mesenteric microcirculation of spontaneously hypertensive rats (SHR) in the early and established stages of hypertension and in normotensive Winstar and Wistar-Kyoto controls (NCR) of comparable age. To assess the amount of active VSM tone in mesenteric arteries and veins and to evaluate tissue perfusion in SHR and NCR, the following parameters will be measured directly: 1) microvessel dimensions (diameters and wall thickness), 2) VSM membrane potentials (Em), 3) intravascular pressure, 4) microvessel blood flow velocity, and 5) tissue and perivascular PO2. Tangential wall stress and volume flow in microvessels will also be calculated. Oxygen availability to the tissue will be controlled by suffusing the preparation with physiological salt solution equilibrated with high and low 02 gas mixtures. The interaction between neural control and local metabolic and myogenic autoregulatory mechanisms will be tested by comparing microcirculatory responses to high and low 02 suffusion, single vessel occlusion (upstream and downstream and electrical stimulation of the perivascular nerve supply. To clarify the mechanisms contributing to VSM tone in SHR and NCR, indices of VSM tone and tissue perfusion will be compared in the presence of specific pharmacological blocking agents and following maximal vasodilation. The influence of adrenergic nerve terminals on in vitro Em and VSM tension will be evaluated and dose response curves to angiotension, K ion, Ca2 ion and perivascular electrical stimulation will be determined in vitro before and after chemical denervation and before and after alpha-and beta-adrenergic blockade.